P-loop containing Nucleoside Triphosphate Hydrolases; Members of the P-loop NTPase domain superfamily are characterized by a conserved nucleotide phosphate-binding motif, also referred to as the Walker A motif (GxxxxGK[S/T], where x is any residue), and the Walker B motif (hhhh[D/E], where h is a hydrophobic residue). The Walker A and B motifs bind the beta-gamma phosphate moiety of the bound nucleotide (typically ATP or GTP) and the Mg2+ cation, respectively. The P-loop NTPases are involved in diverse cellular functions, and they can be divided into two major structural classes: the KG (kinase-GTPase) class which includes Ras-like GTPases and its circularly permutated YlqF-like; and the ASCE (additional strand catalytic E) class which includes ATPase Binding Cassette (ABC), DExD/H-like helicases, 4Fe-4S iron sulfur cluster binding proteins of NifH family, RecA-like F1-ATPases, and ATPases Associated with a wide variety of Activities (AAA). Also included are a diverse set of nucleotide/nucleoside kinase families.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17551122  25 CKIIVVGAKNAGKSTFIERVEFGKFHEEkqteklyrviakkvFEQTLTVELIEKDLggltnEDNG--------------- 89
Cdd:cd00154   1 FKIVLIGDSGVGKTSLLLRFVDNKFSEN--------------YKSTIGVDFKSKTI-----EVDGkkvklqiwdtagqer 61

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17551122  90 FK---KTEMRDVDAVLLFYAADDLESFKQLKENLVHVQRKIPPNANITVVGTKAD-VKEMQVQWQEVDSFAENQGFSCFE 165
Cdd:cd00154  62 FRsitSSYYRGAHGAILVYDVTNRESFENLDKWLNELKEYAPPNIPIILVGNKSDlEDERQVSTEEAQQFAKENGLLFFE 141

                       170
                ....*....|....*...
gi 17551122 166 TSSKTGVNVEIILHDILE 183
Cdd:cd00154 142 TSAKTGENVDEAFESLAR 159

Ras-related in brain (Rab) family of small guanosine triphosphatases (GTPases); Rab GTPases form the largest family within the Ras superfamily. There are at least 60 Rab genes in the human genome, and a number of Rab GTPases are conserved from yeast to humans. Rab GTPases are small, monomeric proteins that function as molecular switches to regulate vesicle trafficking pathways. The different Rab GTPases are localized to the cytosolic face of specific intracellular membranes, where they regulate distinct steps in membrane traffic pathways. In the GTP-bound form, Rab GTPases recruit specific sets of effector proteins onto membranes. Through their effectors, Rab GTPases regulate vesicle formation, actin- and tubulin-dependent vesicle movement, and membrane fusion. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which mask C-terminal lipid binding and promote cytosolic localization. While most unicellular organisms possess 5-20 Rab members, several have been found to possess 60 or more Rabs; for many of these Rab isoforms, homologous proteins are not found in other organisms. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Since crystal structures often lack C-terminal residues, the lipid modification site is not available for annotation in many of the CDs in the hierarchy, but is included where possible.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17551122  25 CKIIVVGAKNAGKSTFIERVEFGKFHEEkqteklyrviakkvFEQTLTVELIEKDLggltnEDNG--------------- 89
Cdd:cd00154   1 FKIVLIGDSGVGKTSLLLRFVDNKFSEN--------------YKSTIGVDFKSKTI-----EVDGkkvklqiwdtagqer 61

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17551122  90 FK---KTEMRDVDAVLLFYAADDLESFKQLKENLVHVQRKIPPNANITVVGTKAD-VKEMQVQWQEVDSFAENQGFSCFE 165
Cdd:cd00154  62 FRsitSSYYRGAHGAILVYDVTNRESFENLDKWLNELKEYAPPNIPIILVGNKSDlEDERQVSTEEAQQFAKENGLLFFE 141

                       170
                ....*....|....*...
gi 17551122 166 TSSKTGVNVEIILHDILE 183
Cdd:cd00154 142 TSAKTGENVDEAFESLAR 159

Rab subfamily of small GTPases; Rab GTPases are implicated in vesicle trafficking.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17551122     26 KIIVVGAKNAGKSTFIERVEFGKFHEEkqteklyrviakkvFEQTLTVELIEKDLgglTNEDngfKKTEM---------- 95
Cdd:smart00175   2 KIILIGDSGVGKSSLLSRFTDGKFSEQ--------------YKSTIGVDFKTKTI---EVDG---KRVKLqiwdtagqer 61

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17551122     96 ---------RDVDAVLLFYAADDLESFKQLKENLVHVQRKIPPNANITVVGTKADVKEM-QVQWQEVDSFAENQGFSCFE 165
Cdd:smart00175  62 frsitssyyRGAVGALLVYDITNRESFENLENWLKELREYASPNVVIMLVGNKSDLEEQrQVSREEAEAFAEEHGLPFFE 141

                          170       180
                   ....*....|....*....|...
gi 17551122    166 TSSKTGVNVEIILHDILETIFER 188
Cdd:smart00175 142 TSAKTNTNVEEAFEELAREILKR 164

Rab GTPase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17551122   26 KIIVVGAKNAGKSTFIERVEFGKFH-EEKQTeklyrvIAKKVFEQTLTVE--LIEKDLGGLTNEDN--GFKKTEMRDVDA 100
Cdd:PLN03110  14 KIVLIGDSGVGKSNILSRFTRNEFClESKST------IGVEFATRTLQVEgkTVKAQIWDTAGQERyrAITSAYYRGAVG 87

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17551122  101 VLLFYAADDLESFKQLKENLVHVQRKIPPNANITVVGTKADVKEMQ-VQWQEVDSFAENQGFSCFETSSKTGVNVE---- 175
Cdd:PLN03110  88 ALLVYDITKRQTFDNVQRWLRELRDHADSNIVIMMAGNKSDLNHLRsVAEEDGQALAEKEGLSFLETSALEATNVEkafq 167

                        170       180       190
                 ....*....|....*....|....*....|...
gi 17551122  176 IILHDILETIFERRFASDDDEVLSNQPVYASTV 208
Cdd:PLN03110 168 TILLEIYHIISKKALAAQEAAANSGLPGQGTTI 200

Ras-related in brain (Rab) family of small guanosine triphosphatases (GTPases); Rab GTPases form the largest family within the Ras superfamily. There are at least 60 Rab genes in the human genome, and a number of Rab GTPases are conserved from yeast to humans. Rab GTPases are small, monomeric proteins that function as molecular switches to regulate vesicle trafficking pathways. The different Rab GTPases are localized to the cytosolic face of specific intracellular membranes, where they regulate distinct steps in membrane traffic pathways. In the GTP-bound form, Rab GTPases recruit specific sets of effector proteins onto membranes. Through their effectors, Rab GTPases regulate vesicle formation, actin- and tubulin-dependent vesicle movement, and membrane fusion. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which mask C-terminal lipid binding and promote cytosolic localization. While most unicellular organisms possess 5-20 Rab members, several have been found to possess 60 or more Rabs; for many of these Rab isoforms, homologous proteins are not found in other organisms. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Since crystal structures often lack C-terminal residues, the lipid modification site is not available for annotation in many of the CDs in the hierarchy, but is included where possible.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17551122  25 CKIIVVGAKNAGKSTFIERVEFGKFHEEkqteklyrviakkvFEQTLTVELIEKDLggltnEDNG--------------- 89
Cdd:cd00154   1 FKIVLIGDSGVGKTSLLLRFVDNKFSEN--------------YKSTIGVDFKSKTI-----EVDGkkvklqiwdtagqer 61

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17551122  90 FK---KTEMRDVDAVLLFYAADDLESFKQLKENLVHVQRKIPPNANITVVGTKAD-VKEMQVQWQEVDSFAENQGFSCFE 165
Cdd:cd00154  62 FRsitSSYYRGAHGAILVYDVTNRESFENLDKWLNELKEYAPPNIPIILVGNKSDlEDERQVSTEEAQQFAKENGLLFFE 141

                       170
                ....*....|....*...
gi 17551122 166 TSSKTGVNVEIILHDILE 183
Cdd:cd00154 142 TSAKTGENVDEAFESLAR 159

Ras family; Includes sub-families Ras, Rab, Rac, Ral, Ran, Rap Ypt1 and more. Shares P-loop motif with GTP_EFTU, arf and myosin_head. See pfam00009 pfam00025, pfam00063. As regards Rab GTPases, these are important regulators of vesicle formation, motility and fusion. They share a fold in common with all Ras GTPases: this is a six-stranded beta-sheet surrounded by five alpha-helices.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17551122    26 KIIVVGAKNAGKSTFIERVEFGKFHEEkqteklyrviakkvFEQTLTVELIEKDLggltNEDNGFKKTE----------- 94
Cdd:pfam00071   1 KLVLVGDGGVGKSSLLIRFTQNKFPEE--------------YIPTIGVDFYTKTI----EVDGKTVKLQiwdtagqerfr 62

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17551122    95 ------MRDVDAVLLFYAADDLESFKQLKENLVHVQRKIPPNANITVVGTKADVKEM-QVQWQEVDSFAENQGFSCFETS 167
Cdd:pfam00071  63 alrplyYRGADGFLLVYDITSRDSFENVKKWVEEILRHADENVPIVLVGNKCDLEDQrVVSTEEGEALAKELGLPFMETS 142

                         170       180
                  ....*....|....*....|
gi 17551122   168 SKTGVNVEIILHDILETIFE 187
Cdd:pfam00071 143 AKTNENVEEAFEELAREILK 162

Rat sarcoma (Ras) family of small guanosine triphosphatases (GTPases); The Ras family of the Ras superfamily includes classical N-Ras, H-Ras, and K-Ras, as well as R-Ras, Rap, Ral, Rheb, Rhes, ARHI, RERG, Rin/Rit, RSR1, RRP22, Ras2, Ras-dva, and RGK proteins. Ras proteins regulate cell growth, proliferation and differentiation. Ras is activated by guanine nucleotide exchange factors (GEFs) that release GDP and allow GTP binding. Many RasGEFs have been identified. These are sequestered in the cytosol until activation by growth factors triggers recruitment to the plasma membrane or Golgi, where the GEF colocalizes with Ras. Active GTP-bound Ras interacts with several effector proteins: among the best characterized are the Raf kinases, phosphatidylinositol 3-kinase (PI3K), RalGEFs and NORE/MST1. Most Ras proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Ras proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17551122  26 KIIVVGAKNAGKSTFIERVEFGKFHEEKQ--TEKLYRviakKVFE---QTLTVELIekDLGGlTNEDNGFKKTEMRDVDA 100
Cdd:cd00876   1 KLVVLGAGGVGKSALTIRFVSGEFVEEYDptIEDSYR----KQIVvdgETYTLDIL--DTAG-QEEFSAMRDQYIRNGDG 73

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17551122 101 VLLFYAADDLESF---KQLKENLVHV-QRKIPPnanITVVGTKAD-VKEMQVQWQEVDSFAENQGFSCFETSSKTGVNVE 175
Cdd:cd00876  74 FILVYSITSRESFeeiKNIREQILRVkDKEDVP---IVLVGNKCDlENERQVSTEEGEALAEEWGCPFLETSAKTNINID 150

                ....*..
gi 17551122 176 IILHDIL 182
Cdd:cd00876 151 ELFNTLV 157

Ral (Ras-like) family containing highly homologous RalA and RalB; The Ral (Ras-like) subfamily consists of the highly homologous RalA and RalB. Ral proteins are believed to play a crucial role in tumorigenesis, metastasis, endocytosis, and actin cytoskeleton dynamics. Despite their high sequence similarity (>80% sequence identity), nonoverlapping and opposing functions have been assigned to RalA and RalBs in tumor migration. In human bladder and prostate cancer cells, RalB promotes migration while RalA inhibits it. A Ral-specific set of GEFs has been identified that are activated by Ras binding. This RalGEF activity is enhanced by Ras binding to another of its target proteins, phosphatidylinositol 3-kinase (PI3K). Ral effectors include RLIP76/RalBP1, a Rac/cdc42 GAP, and the exocyst (Sec6/8) complex, a heterooctomeric protein complex that is involved in tethering vesicles to specific sites on the plasma membrane prior to exocytosis. In rat kidney cells, RalB is required for functional assembly of the exocyst and for localizing the exocyst to the leading edge of migrating cells. In human cancer cells, RalA is required to support anchorage-independent proliferation and RalB is required to suppress apoptosis. RalA has been shown to localize to the plasma membrane while RalB is localized to the intracellular vesicles. Most Ras proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Ras proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17551122  26 KIIVVGAKNAGKSTFIERVEFGKFHEEKQTEKL--YRviaKKVFEQTLTVELIEKDLGGltNED-NGFKKTEMRDVDAVL 102
Cdd:cd04139   2 KVIMVGSGGVGKSALTLQFMYDEFVEDYEPTKAdsYR---KKVVLDGEEVQLNILDTAG--QEDyAAIRDNYFRSGEGFL 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17551122 103 LFYAADDLESFKQLKENLVHVQR-KIPPNANITVVGTKADVKEM-QVQWQEVDSFAENQGFSCFETSSKTGVNVEIILHD 180
Cdd:cd04139  77 LVFSITDMESFTALAEFREQILRvKEDDNVPLLLVGNKCDLEDKrQVSVEEAANLAEQWGVNYVETSAKTRANVDKVFFD 156

                ....*
gi 17551122 181 ILETI 185
Cdd:cd04139 157 LVREI 161

Rab GTPase family 21 (Rab21); The localization and function of Rab21 are not clearly defined, with conflicting data reported. Rab21 has been reported to localize in the ER in human intestinal epithelial cells, with partial colocalization with alpha-glucosidase, a late endosomal/lysosomal marker. More recently, Rab21 was shown to colocalize with and affect the morphology of early endosomes. In Dictyostelium, GTP-bound Rab21, together with two novel LIM domain proteins, LimF and ChLim, has been shown to regulate phagocytosis. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17551122  96 RDVDAVLLFYAADDLESF---KQLKENLVHVQRKippNANITVVGTKAD-VKEMQVQWQEVDSFAENQGFSCFETSSKTG 171
Cdd:cd04123  71 RDADGAILVYDITDADSFqkvKKWIKELKQMRGN---NISLVIVGNKIDlERQRVVSKSEAEEYAKSVGAKHFETSAKTG 147

                        90
                ....*....|....
gi 17551122 172 VNVEIILHDILETI 185
Cdd:cd04123 148 KGIEELFLSLAKRM 161

Rab GTPase family 24 (Rab24); Rab24 is distinct from other Rabs in several ways. It exists primarily in the GTP-bound state, having a low intrinsic GTPase activity; it is not efficiently geranyl-geranylated at the C-terminus; it does not form a detectable complex with Rab GDP-dissociation inhibitors (GDIs); and it has recently been shown to undergo tyrosine phosphorylation when overexpressed in vitro. The specific function of Rab24 still remains unknown. It is found in a transport route between ER-cis-Golgi and late endocytic compartments. It is putatively involved in an autophagic pathway, possibly directing misfolded proteins in the ER to degradative pathways. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17551122  26 KIIVVGAKNAGKSTFIERVEFGKF-HEEKQTEKLYRVIAKKVFEQTLTVELIEKDLGGlTNEDNGFKKTEMRDVDAVLLF 104
Cdd:cd04118   2 KVVMLGKESVGKTSLVERYVHHRFlVGPYQNTIGAAFVAKRMVVGERVVTLGIWDTAG-SERYEAMSRIYYRGAKAAIVC 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17551122 105 YAADDLESFKQLKENLVHVQrKIPPNANITVVGTKADVKEM-----QVQWQEVDSFAENQGFSCFETSSKTGVNVEIILH 179
Cdd:cd04118  81 YDLTDSSSFERAKFWVKELQ-NLEEHCKIYLCGTKSDLIEQdrslrQVDFHDVQDFADEIKAQHFETSSKTGQNVDELFQ 159

                ....
gi 17551122 180 DILE 183
Cdd:cd04118 160 KVAE 163

Rab GTPase family 39 (Rab39); Found in eukaryotes, Rab39 is mainly found in epithelial cell lines, but is distributed widely in various human tissues and cell lines. It is believed to be a novel Rab protein involved in regulating Golgi-associated vesicular transport during cellular endocytosis. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17551122  26 KIIVVGAKNAGKSTFIERVEFGKFHEekqteklyrviakkVFEQTLTVE----LIEKDLGGL-------TNEDNGFK--- 91
Cdd:cd04111   4 RLIVIGDSTVGKSSLLKRFTEGRFAE--------------VSDPTVGVDffsrLIEIEPGVRiklqlwdTAGQERFRsit 69

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17551122  92 KTEMRDVDAVLLFYAADDLESFKQLKENLVHVQRKIPPNANI-TVVGTKADVK-EMQVQWQEVDSFAENQGFSCFETSSK 169
Cdd:cd04111  70 RSYYRNSVGVLLVFDITNRESFEHVHDWLEEARSHIQPHRPVfILVGHKCDLEsQRQVTREEAEKLAKDLGMKYIETSAR 149

                       170
                ....*....|....*....
gi 17551122 170 TGVNVEIILHDILETIFER 188
Cdd:cd04111 150 TGDNVEEAFELLTQEIYER 168

Ras - dorsal-ventral anterior localization (Ras-dva) family; Ras-dva subfamily. Ras-dva (Ras - dorsal-ventral anterior localization) subfamily consists of a set of proteins characterized only in Xenopus leavis, to date. In Xenopus Ras-dva expression is activated by the transcription factor Otx2 and begins during gastrulation throughout the anterior ectoderm. Ras-dva expression is inhibited in the anterior neural plate by factor Xanf1. Downregulation of Ras-dva results in head development abnormalities through the inhibition of several regulators of the anterior neural plate and folds patterning, including Otx2, BF-1, Xag2, Pax6, Slug, and Sox9. Downregulation of Ras-dva also interferes with the FGF-8a signaling within the anterior ectoderm. Most Ras proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Ras proteins.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17551122  26 KIIVVGAKNAGKSTFIERVEFGKFHEE--KQTEKLYRvIAKKVFEQTLTVELIekDLGGlTNEDNGFKKTEMRDVDAVLL 103
Cdd:cd04147   1 RLVFMGAAGVGKTALIQRFLYDTFEPKhrRTVEELHS-KEYEVAGVKVTIDIL--DTSG-SYSFPAMRKLSIQNGDAFAL 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17551122 104 FYAADDLESF---KQLKENLVHVQR-KIPPnanITVVGTKAD-VKEMQVQWQEVDSFAENQGFSCF-ETSSKTGVNVEII 177
Cdd:cd04147  77 VYSVDDPESFeevKRLREEILEVKEdKFVP---IVVVGNKIDsLAERQVEAADALSTVELDWNNGFvEASAKDNENVTEV 153

                ....*
gi 17551122 178 LHDIL 182
Cdd:cd04147 154 FKELL 158

Rab GTPase family 1 includes the yeast homolog Ypt1; Rab1/Ypt1 subfamily. Rab1 is found in every eukaryote and is a key regulatory component for the transport of vesicles from the ER to the Golgi apparatus. Studies on mutations of Ypt1, the yeast homolog of Rab1, showed that this protein is necessary for the budding of vesicles of the ER as well as for their transport to, and fusion with, the Golgi apparatus. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17551122  96 RDVDAVLLFYAADDLESFKQLKENLVHVQRKIPPNANITVVGTKADVKEMQ-VQWQEVDSFAENQGFSCFETSSKTGVNV 174
Cdd:cd01869  73 RGAHGIIIVYDVTDQESFNNVKQWLQEIDRYASENVNKLLVGNKCDLTDKKvVDYTEAKEFADELGIPFLETSAKNATNV 152

                        90
                ....*....|....
gi 17551122 175 EIILHDILETIFER 188
Cdd:cd01869 153 EEAFMTMAREIKKR 166

Rab GTPase family 4 (Rab4); Rab4 subfamily. Rab4 has been implicated in numerous functions within the cell. It helps regulate endocytosis through the sorting, recycling, and degradation of early endosomes. Mammalian Rab4 is involved in the regulation of many surface proteins including G-protein-coupled receptors, transferrin receptor, integrins, and surfactant protein A. Experimental data implicate Rab4 in regulation of the recycling of internalized receptors back to the plasma membrane. It is also believed to influence receptor-mediated antigen processing in B-lymphocytes, in calcium-dependent exocytosis in platelets, in alpha-amylase secretion in pancreatic cells, and in insulin-induced translocation of Glut4 from internal vesicles to the cell surface. Rab4 is known to share effector proteins with Rab5 and Rab11. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17551122  26 KIIVVGAKNAGKSTFIERVEFGKFHEEKQTEKLYRVIAKKVFEQTLTVELIEKDLGGLTNedngFK---KTEMRDVDAVL 102
Cdd:cd04113   2 KFLIIGSAGTGKSCLLHQFIENKFKQDSNHTIGVEFGSRVVNVGGKSVKLQIWDTAGQER----FRsvtRSYYRGAAGAL 77

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 17551122 103 LFYAADDLESFKQLKENLVHVQRKIPPNANITVVGTKADVKE-MQVQWQEVDSFAENQGFSCFETSSKTGVNVE 175
Cdd:cd04113  78 LVYDITSRESFNALTNWLTDARTLASPDIVIILVGNKKDLEDdREVTFLEASRFAQENGLLFLETSALTGENVE 151

Rab GTPase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17551122   26 KIIVVGAKNAGKSTFIERVEFGKFH-EEKQTeklyrvIAKKVFEQTLTVE--LIEKDLGGLTNEDN--GFKKTEMRDVDA 100
Cdd:PLN03110  14 KIVLIGDSGVGKSNILSRFTRNEFClESKST------IGVEFATRTLQVEgkTVKAQIWDTAGQERyrAITSAYYRGAVG 87

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17551122  101 VLLFYAADDLESFKQLKENLVHVQRKIPPNANITVVGTKADVKEMQ-VQWQEVDSFAENQGFSCFETSSKTGVNVE---- 175
Cdd:PLN03110  88 ALLVYDITKRQTFDNVQRWLRELRDHADSNIVIMMAGNKSDLNHLRsVAEEDGQALAEKEGLSFLETSALEATNVEkafq 167

                        170       180       190
                 ....*....|....*....|....*....|...
gi 17551122  176 IILHDILETIFERRFASDDDEVLSNQPVYASTV 208
Cdd:PLN03110 168 TILLEIYHIISKKALAAQEAAANSGLPGQGTTI 200

Ras subfamily of RAS small GTPases; Similar in fold and function to the bacterial EF-Tu GTPase. p21Ras couples receptor Tyr kinases and G protein receptors to protein kinase cascades

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17551122     26 KIIVVGAKNAGKST----FIErvefGKFHEE----------KQTEklyrviakkVFEQTLTVELIekDLGGlTNEDNGFK 91
Cdd:smart00173   2 KLVVLGSGGVGKSAltiqFIQ----GHFVDDydptiedsyrKQIE---------IDGEVCLLDIL--DTAG-QEEFSAMR 65

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17551122     92 KTEMRDVDAVLLFYAADDLESF---KQLKENLVHVQRK--IPpnanITVVGTKADVK-EMQVQWQEVDSFAENQGFSCFE 165
Cdd:smart00173  66 DQYMRTGEGFLLVYSITDRQSFeeiKKFREQILRVKDRddVP----IVLVGNKCDLEsERVVSTEEGKELARQWGCPFLE 141

                          170       180
                   ....*....|....*....|
gi 17551122    166 TSSKTGVNVEIILHDILETI 185
Cdd:smart00173 142 TSAKERVNVDEAFYDLVREI 161

Small GTPase of the Ras superfamily; ill-defined subfamily; SMART predicts Ras-like small GTPases of the ARF, RAB, RAN, RAS, and SAR subfamilies. Others that could not be classified in this way are predicted to be members of the small GTPase superfamily without predictions of the subfamily.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17551122     26 KIIVVGAKNAGKST----FIErvefGKFHEE----------KQTEklyrviakkVFEQTLTVELIekDLGGlTNEDNGFK 91
Cdd:smart00010   4 KLVVLGGGGVGKSAltiqFVQ----GHFVDEydptiedsyrKQIE---------IDGEVCLLDIL--DTAG-QEEFSAMR 67

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17551122     92 KTEMRDVDAVLLFYAADDLESF---KQLKENLVHVQRK--IPpnanITVVGTKADVK-EMQVQWQEVDSFAENQGFSCFE 165
Cdd:smart00010  68 DQYMRTGEGFLLVYSITDRQSFeeiAKFREQILRVKDRddVP----IVLVGNKCDLEnERVVSTEEGKELARQWGCPFLE 143

                          170       180
                   ....*....|....*....|
gi 17551122    166 TSSKTGVNVEIILHDILETI 185
Cdd:smart00010 144 TSAKERINVDEAFYDLVREI 163

Rab GTPase families 8, 10, 13 (Rab8, Rab10, Rab13); Rab8/Sec4/Ypt2 are known or suspected to be involved in post-Golgi transport to the plasma membrane. It is likely that these Rabs have functions that are specific to the mammalian lineage and have no orthologs in plants. Rab8 modulates polarized membrane transport through reorganization of actin and microtubules, induces the formation of new surface extensions, and has an important role in directed membrane transport to cell surfaces. The Ypt2 gene of the fission yeast Schizosaccharomyces pombe encodes a member of the Ypt/Rab family of small GTP-binding proteins, related in sequence to Sec4p of Saccharomyces cerevisiae but closer to mammalian Rab8. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 17551122 101 VLLFYAADDLESFKQLKENLVHVQRKIPPNANITVVGTKADVKE-MQVQWQEVDSFAENQGFSCFETSSKTGVNVE 175
Cdd:cd01867  79 IILVYDITDEKSFENIKNWMRNIDEHASEDVERMLVGNKCDMEEkRVVSKEEGEALAREYGIKFLETSAKANINVE 154

Rab GTPase family 14 (Rab14); Rab14 GTPases are localized to biosynthetic compartments, including the rough ER, the Golgi complex, and the trans-Golgi network, and to endosomal compartments, including early endosomal vacuoles and associated vesicles. Rab14 is believed to function in both the biosynthetic and recycling pathways between the Golgi and endosomal compartments. Rab14 has also been identified on GLUT4 vesicles, and has been suggested to help regulate GLUT4 translocation. In addition, Rab14 is believed to play a role in the regulation of phagocytosis. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17551122  96 RDVDAVLLFYAADDLESFKQLKENLVHVQRKIPPNANITVVGTKADVKEMQ-VQWQEVDSFAENQGFSCFETSSKTGVNV 174
Cdd:cd04122  73 RGAAGALMVYDITRRSTYNHLSSWLTDARNLTNPNTVIFLIGNKADLEAQRdVTYEEAKQFADENGLLFLECSAKTGENV 152

                        90
                ....*....|...
gi 17551122 175 EIILHDILETIFE 187
Cdd:cd04122 153 EDAFLETAKKIYQ 165

Rab GTPase family 26 (Rab26); Rab26 subfamily. First identified in rat pancreatic acinar cells, Rab26 is believed to play a role in recruiting mature granules to the plasma membrane upon beta-adrenergic stimulation. Rab26 belongs to the Rab functional group III, which are considered key regulators of intracellular vesicle transport during exocytosis. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17551122  96 RDVDAVLLFYAADDLESFKQLKENLVHVQRKIPPNANITVVGTKADVK-EMQVQWQEVDSFAENQGFSCFETSSKTGVNV 174
Cdd:cd04112  72 RDAHALLLLYDVTNKSSFDNIRAWLTEILEYAQSDVVIMLLGNKADMSgERVVKREDGERLAKEYGVPFMETSAKTGLNV 151

                        90       100
                ....*....|....*....|.
gi 17551122 175 EIILHDILETIFERRFASDDD 195
Cdd:cd04112 152 ELAFTAVAKELKHRSVEQPDE 172

Rab GTPase family 3 contains Rab3A, Rab3B, Rab3C and Rab3D; The Rab3 subfamily contains Rab3A, Rab3B, Rab3C, and Rab3D. All four isoforms were found in mouse brain and endocrine tissues, with varying levels of expression. Rab3A, Rab3B, and Rab3C localized to synaptic and secretory vesicles; Rab3D was expressed at high levels only in adipose tissue, exocrine glands, and the endocrine pituitary, where it is localized to cytoplasmic secretory granules. Rab3 appears to control Ca2+-regulated exocytosis. The appropriate GDP/GTP exchange cycle of Rab3A is required for Ca2+-regulated exocytosis to occur, and interaction of the GTP-bound form of Rab3A with effector molecule(s) is widely believed to be essential for this process. Functionally, most studies point toward a role for Rab3 in the secretion of hormones and neurotransmitters. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17551122  26 KIIVVGAKNAGKSTFIERVEFGKFHEEKQTEKLYRVIAKKVFEQTLTVELIEKDLGGlTNEDNGFKKTEMRDVDAVLLFY 105
Cdd:cd01865   3 KLLIIGNSSVGKTSFLFRYADDSFTSAFVSTVGIDFKVKTVYRNDKRIKLQIWDTAG-QERYRTITTAYYRGAMGFILMY 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17551122 106 AADDLESFKQLKENLVHVQRKIPPNANITVVGTKADVK-EMQVQWQEVDSFAENQGFSCFETSSKTGVNVEIILHDILET 184
Cdd:cd01865  82 DITNEESFNAVQDWSTQIKTYSWDNAQVILVGNKCDMEdERVVSAERGRQLADQLGFEFFEASAKENINVKQVFERLVDI 161

                ....
gi 17551122 185 IFER 188
Cdd:cd01865 162 ICDK 165

Rab GTPase family 2 (Rab2); Rab2 is localized on cis-Golgi membranes and interacts with Golgi matrix proteins. Rab2 is also implicated in the maturation of vesicular tubular clusters (VTCs), which are microtubule-associated intermediates in transport between the ER and Golgi apparatus. In plants, Rab2 regulates vesicle trafficking between the ER and the Golgi bodies and is important to pollen tube growth. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17551122  96 RDVDAVLLFYAADDLESFKQLKENLVHVQRKIPPNANITVVGTKADV-KEMQVQWQEVDSFAENQGFSCFETSSKTGVNV 174
Cdd:cd01866  75 RGAAGALLVYDITRRETFNHLTSWLEDARQHSNSNMTIMLIGNKCDLeSRREVSYEEGEAFAREHGLIFMETSAKTASNV 154

                        90
                ....*....|....
gi 17551122 175 EIILHDILETIFER 188
Cdd:cd01866 155 EEAFINTAKEIYDK 168

Rab family protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17551122   96 RDVDAVLLFYAADDLESFKQLKENLVHVQRKIPPNANITVVGTKADVKEMQ-VQWQEVDSFAENQGFSCFETSSKTGVNV 174
Cdd:PLN03108  77 RGAAGALLVYDITRRETFNHLASWLEDARQHANANMTIMLIGNKCDLAHRRaVSTEEGEQFAKEHGLIFMEASAKTAQNV 156